Prostaglandin E Synthases in Zebrafish

OBJECTIVE—Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE2 formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize...

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Veröffentlicht in:Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2005-02, Vol.25 (2), p.315-320
Hauptverfasser: Pini, Barbara, Grosser, Tilo, Lawson, John A, Price, Tom S, Pack, Michael A, FitzGerald, Garret A
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container_end_page 320
container_issue 2
container_start_page 315
container_title Arteriosclerosis, thrombosis, and vascular biology
container_volume 25
creator Pini, Barbara
Grosser, Tilo
Lawson, John A
Price, Tom S
Pack, Michael A
FitzGerald, Garret A
description OBJECTIVE—Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE2 formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish. METHODS AND RESULTS—We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development. CONCLUSIONS—mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors.
doi_str_mv 10.1161/01.ATV.0000152355.97808.10
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Located downstream of the cyclooxygenases, PGESs catalyze PGE2 formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish. METHODS AND RESULTS—We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development. CONCLUSIONS—mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000152355.97808.10</identifier><identifier>PMID: 15576635</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Vessels - embryology ; Blood Vessels - enzymology ; Blood Vessels - growth &amp; development ; Cardiology. Vascular system ; Chromosome Mapping ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Embryo, Nonmammalian ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Intramolecular Oxidoreductases - biosynthesis ; Intramolecular Oxidoreductases - genetics ; Isoenzymes - biosynthesis ; Isoenzymes - genetics ; Kidney - embryology ; Kidney - enzymology ; Kidney - growth &amp; development ; Larva ; Medical sciences ; Microsomes - enzymology ; Molecular Sequence Data ; Organ Specificity ; Phylogeny ; Prostaglandin-E Synthases ; Prostaglandin-Endoperoxide Synthases - biosynthesis ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandins E - biosynthesis ; Semicircular Canals - embryology ; Semicircular Canals - enzymology ; Semicircular Canals - growth &amp; development ; Zebrafish - growth &amp; development ; Zebrafish - metabolism ; Zebrafish Proteins - biosynthesis ; Zebrafish Proteins - genetics</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2005-02, Vol.25 (2), p.315-320</ispartof><rights>2005 American Heart Association, Inc.</rights><rights>2005 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. 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Vascular system</topic><topic>Chromosome Mapping</topic><topic>Cyclooxygenase 1</topic><topic>Cyclooxygenase 2</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Embryo, Nonmammalian</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Intramolecular Oxidoreductases - biosynthesis</topic><topic>Intramolecular Oxidoreductases - genetics</topic><topic>Isoenzymes - biosynthesis</topic><topic>Isoenzymes - genetics</topic><topic>Kidney - embryology</topic><topic>Kidney - enzymology</topic><topic>Kidney - growth &amp; development</topic><topic>Larva</topic><topic>Medical sciences</topic><topic>Microsomes - enzymology</topic><topic>Molecular Sequence Data</topic><topic>Organ Specificity</topic><topic>Phylogeny</topic><topic>Prostaglandin-E Synthases</topic><topic>Prostaglandin-Endoperoxide Synthases - biosynthesis</topic><topic>Prostaglandin-Endoperoxide Synthases - genetics</topic><topic>Prostaglandins E - biosynthesis</topic><topic>Semicircular Canals - embryology</topic><topic>Semicircular Canals - enzymology</topic><topic>Semicircular Canals - growth &amp; development</topic><topic>Zebrafish - growth &amp; development</topic><topic>Zebrafish - metabolism</topic><topic>Zebrafish Proteins - biosynthesis</topic><topic>Zebrafish Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pini, Barbara</creatorcontrib><creatorcontrib>Grosser, Tilo</creatorcontrib><creatorcontrib>Lawson, John A</creatorcontrib><creatorcontrib>Price, Tom S</creatorcontrib><creatorcontrib>Pack, Michael A</creatorcontrib><creatorcontrib>FitzGerald, Garret A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pini, Barbara</au><au>Grosser, Tilo</au><au>Lawson, John A</au><au>Price, Tom S</au><au>Pack, Michael A</au><au>FitzGerald, Garret A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prostaglandin E Synthases in Zebrafish</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2005-02</date><risdate>2005</risdate><volume>25</volume><issue>2</issue><spage>315</spage><epage>320</epage><pages>315-320</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE2 formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish. METHODS AND RESULTS—We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development. CONCLUSIONS—mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>15576635</pmid><doi>10.1161/01.ATV.0000152355.97808.10</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Blood Vessels - embryology
Blood Vessels - enzymology
Blood Vessels - growth & development
Cardiology. Vascular system
Chromosome Mapping
Cyclooxygenase 1
Cyclooxygenase 2
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Intramolecular Oxidoreductases - biosynthesis
Intramolecular Oxidoreductases - genetics
Isoenzymes - biosynthesis
Isoenzymes - genetics
Kidney - embryology
Kidney - enzymology
Kidney - growth & development
Larva
Medical sciences
Microsomes - enzymology
Molecular Sequence Data
Organ Specificity
Phylogeny
Prostaglandin-E Synthases
Prostaglandin-Endoperoxide Synthases - biosynthesis
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandins E - biosynthesis
Semicircular Canals - embryology
Semicircular Canals - enzymology
Semicircular Canals - growth & development
Zebrafish - growth & development
Zebrafish - metabolism
Zebrafish Proteins - biosynthesis
Zebrafish Proteins - genetics
title Prostaglandin E Synthases in Zebrafish
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